Isolated ApoA-I gene regulatory sequence elements

Abstract

The present invention provides isolated apolipoprotein transcription factors and gene regulatory elements. The invention also provides methods of modulating apolipoprotein gene expression by interfering with interactions between apolipoprotein transcription factors and their cognate regulatory elements and/or by interfering with protein-protein interactions between or among apolipoprotein transcription factors or between an apolipoprotein transcription factor and the transcription machinery. This invention has application in the treatment of disorders relating to lipid metabolism (e.g. atherosclerosis, hypertriglyceridemia, etc.).

We claim: 
     
       1. An isolated apoA-I gene regulatory sequence element having a nucleotide sequence consisting of the sequence found between nucleotide number 212 and nucleotide number 250 of SEQ ID NO:10. 
     
     
       2. An isolated apoA-I gene regulatory sequence element having a nucleotide sequence consisting of the sequence found between nucleotide number 106 and nucleotide number 157 of SEQ ID NO:10. 
     
     
       3. An isolated apoA-I gene regulatory sequence element having a nucleotide sequence consisting of the sequence found between nucleotide number 59 and nucleotide number 86 of SEQ ID NO:10. 
     
     
       4. An isolated apoA-I gene regulatory sequence element having a nucleotide sequence consisting of the sequence found between nucleotide number 14 and nucleotide number 44 of SEQ ID NO:10. 
     
     
       5. An oligonucleotide having a nucleotide sequence consisting of the binding site portion of an apoA-I gene regulatory sequence element, which apoA-I gene regulatory sequence element is selected from the group consisting of: element A, consisting of nucleotides 212 to +250 of SEQ ID NO:10;   element B, consisting of nucleotides 106 to 157 of SEQ ID NO:10;   element C, consisting of nucleotides 59 to 86 of SEQ ID NO:10; and   element D, consisting of nucleotides 14 to 44 of SEQ ID NO:10.   
     
     
       6. The oligonucleotide of claim 5, said oligonucleotide being double-stranded. 
     
     
       7. The oligonucleotide of claim 5, said oligonucleotide being single stranded and consisting of the sense strand of said regulatory sequence element. 
     
     
       8. The oligonucleotide of claim 5, said oligonucleotide being single stranded and consisting of the antisense strand of said regulatory sequence element. 
     
     
       9. An oligonucleotide having a nucleotide sequence consisting of multiple copies of the binding site portion of an apoA-I gene regulatory sequence element, which apoA-I gene regulatory sequence element is selected from the group consisting of: element A, consisting of nucleotides 212 to +250 of SEQ ID NO:10;   element B, consisting of nucleotides 106 to 157 of SEQ ID NO:10;   element C, consisting of nucleotides 59 to 86 of SEQ ID NO:10; and   element D, consisting of nucleotides 14 to 44 of SEQ ID NO:10.   
     
     
       10. A recombinant nucleic acid molecule comprising: a gene other than apoA-I operably linked to   an isolated apoA-I gene regulatory sequence element consisting of a nucleotide sequence consisting of a sequence selected from the group consisting of: element A, consisting of nucleotides 212 to +250 of SEQ ID NO:10;   element B, consisting of nucleotides 106 to 157 of SEQ ID NO:10;   element C, consisting of nucleotides 59 to 86 of SEQ ID NO:10; and   element D, consisting of nucleotides 14 to 44 of SEQ ID NO:10; and combinations thereof.